Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

通过骨间充质干细胞（BMSC）和血管内皮细胞（EC）的联合移植可以增强骨组织更新。然而，基于干细胞的疗法存在明显的局限性，阻碍了其临床转化。因此，我们研究了替代干细胞替代品促进骨再生的潜力。在本研究中，我们成功地从BMSCs和ECs中制备了细胞膜囊泡（CMV）。结果表明，BMSC 衍生的细胞膜囊泡 (BMSC-CMV) 具有参与近分泌信号传导的膜受体和源自其亲代细胞的生长因子。 EC 衍生的细胞膜囊泡 (EC-CMV) 还含有源自其亲本细胞的 BMP2 和 VEGF。 BMSC-CMVs增强hUVECs的管形成和迁移能力，而EC-CMVs促进hBMSCs的体外成骨分化。使用大鼠颅骨缺损模型，我们发现 BMSC-CMV 和 EC-CMV 的共移植可以刺激体内血管生成和骨形成。因此，我们的研究可能为骨组织再生的无细胞治疗提供一种创新且可行的方法。